The Effect of Increasing Dialysate Calcium on T50 in Subjects With Secondary Hyperparathyroidism and ESKD (CaT50HD)

The Effect of Increasing Dialysate Calcium on Serum Calcification Propensity in Subjects With Secondary Hyperparathyroidism and End-Stage Kidney Disease

Patients with end-stage kidney disease (ESKD) have an increased risk of cardiovascular mortality. High parathyroid hormone (PTH) from secondary hyperparathyroidism leads to increased efflux of phosphate and calcium from bone, which exacerbates vascular calcification and increases the risk of bone fractures. The main driving factor for secondary hyperparathyroidism is hypocalcaemia caused by low levels of 1,25-dihydroxy vitamin D and pharmacological supplementation with activated vitamin D and oral calcium-containing phosphate-binders are used to control secondary hyperparathyroidism. The amount of calcium used in this context is controversial, as higher calcium load in blood may theoretically increase vascular calcification. Conversely, by alleviating the efflux of phosphate and calcium from bone due to secondary hyperparathyroidism, increasing the load of calcium might actually prevent vascular calcification.

To study this further, we wish to conduct a randomised double-blinded controlled clinical trial of increasing dialysate Ca from 1.25 mmol/L (standard dialysate concentration) to 1.50 mmol/L in patients with ESKD and secondary hyperparathyroidism on maintenance haemodialysis (HD). The overall effect of increased dialysate calcium will be gauged by its effect on serum calcification propensity (T50) and on markers of bone turnover.

Study Overview

• Status: Not yet recruiting
• Conditions: Secondary Hyperparathyroidism; End-stage Kidney Disease
• Intervention / Treatment: Other: Dialysate calcium 1.50 mmol/L

• Study Type: Interventional
• Enrollment (Estimated): 48
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ditte Hansen, MD PhD; Phone Number: +4538682056; Email: ditte.hansen.04@regionh.dk
• Study Contact Backup: Name: Iain Bressendorff, MD PhD; Phone Number: +4524277139; Email: iain.oshoej.bressendorff@regionh.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years.
• Treatment with thrice-weekly maintenance HD for ESKD for > 3 months.
• Dialysate calcium of 1.25 mmol/L (standard concentration).
• Plasma ionised calcium < 1.35 mmol/L (average of last 3 months).
• Plasma intact PTH > 14 ρmol/L.
• Plasma total alkaline phosphatase >90 U/L
• Negative pregnancy test and use of highly effective and safe contraception.
• Able to give written informed consent.

Exclusion Criteria:

• Treatment with peritoneal dialysis.
• Clinical bone fracture within the last 6 months.
• Treatment with bisphosphonates, denosumab, romosozumab, or teriparatide within the last 3 months.
• Other diseases or conditions, which, in the opinion of the site investigator, would prevent participation in or completion of the trial.
• Pregnancy or breastfeeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Dialysate calcium 1.25 mmol/L (standard)	Other: Dialysate calcium 1.50 mmol/L; Increased dialysate calcium of 1.50 mmol/L (as compared to standard dialysate calcium of 1.25 mmol/L)
Experimental: Dialysate calcium 1.50 mmol/L (high)	Other: Dialysate calcium 1.50 mmol/L; Increased dialysate calcium of 1.50 mmol/L (as compared to standard dialysate calcium of 1.25 mmol/L)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in serum calcification propensity (T50)	Between-groups difference in T50 at day 28 adjusted for T50 at day 0	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in bone-specific alkaline phosphatase (bALP)	Between-groups difference in bALP at day 28 adjusted for bALP at day 0	28 days
Difference in procollagen 1 intact N-terminal propeptide (P1NP)	Between-groups difference in P1NP at day 28 adjusted for P1NP at day 0	28 days
Difference in tartrate-resistant acid phosphatase 5b (TRAcP 5b)	Between-groups difference in TRAcP 5b at day 28 adjusted for TRAcP 5b at day 0	28 days
Difference in parathyroid hormone (PTH)	Between-groups difference in PTH at day 28 adjusted for PTH at day 0	28 days
Difference in calciprotein monomers (CPM)	Between-groups difference in CPM at day 28 adjusted for CPM at day 0	28 days
Difference in primary calciprotein particles (CPP-1)	Between-groups difference in CPP-1 at day 28 adjusted for CPP-1 at day 0	28 days
Difference in primary calciprotein particles (CPP-2)	Between-groups difference in CPP-2 at day 28 adjusted for CPP-2 at day 0	28 days
Difference in plasma ionised calcium (iCa)	Between-groups difference in iCa at day 28 adjusted for iCa at day 0	28 days
Difference in plasma phosphate (PO4)	Between-groups difference in PO4 at day 28 adjusted for PO4 at day 0	28 days
Difference in plasma magnesium (Mg)	Between-groups difference in Mg at day 28 adjusted for Mg at day 0	28 days
Difference in all above variables	Within-groups difference in all above variables at day 28 adjusted for values at day 0	28 days

Collaborators and Investigators

• Sponsor: Iain Bressendorff
• Investigators: Principal Investigator: Iain Bressendorff, MD PhD, Herlev and Gentofte Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2024
• Primary Completion (Estimated): August 1, 2025
• Study Completion (Estimated): August 1, 2025

Study Registration Dates

• First Submitted: April 30, 2024
• First Submitted That Met QC Criteria: April 30, 2024
• First Posted (Actual): May 3, 2024

Study Record Updates

• Last Update Posted (Actual): May 3, 2024
• Last Update Submitted That Met QC Criteria: April 30, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Urologic Diseases; Endocrine System Diseases; Disease Attributes; Renal Insufficiency; Parathyroid Diseases; Neoplastic Processes; Renal Insufficiency, Chronic; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Hyperparathyroidism; Neoplasm Metastasis; Kidney Failure, Chronic; Hyperparathyroidism, Secondary; Physiological Effects of Drugs; Calcium-Regulating Hormones and Agents; Pharmaceutical Solutions; Calcium; Dialysis Solutions
• Other Study ID Numbers: CaT50HD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Upon reasonable request to the investigators
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No